- THIS ARTICLE
- Full Text (Rapid PDF)
- Data Supplement
-
All Versions of this Article:
genetics.106.058164v1
175/2/763 most recent - Alert me when this article is cited
- Alert me if a correction is posted
- SERVICES
- Similar articles in this journal
- Similar articles in PubMed
- Alert me to new issues of the journal
- Download to citation manager
- Reprints & Permissions
- CITING ARTICLES
- Citing Articles via HighWire
- Citing Articles via Google Scholar
- GOOGLE SCHOLAR
- Articles by Peng, B.
- Articles by Kimmel, M.
- Search for Related Content
- PUBMED
- PubMed Citation
- Articles by Peng, B.
- Articles by Kimmel, M.
doi:10.1534/genetics.106.058164
A more recent version of this article appeared on February 1, 2007.
REGULAR RESEARCH PAPERS |
Simulations provide support for the common disease common variant hypothesis
Bo Peng 1* and Marek Kimmel 1
1 Rice University
* To whom correspondence should be addressed. E-mail: bpeng{at}rice.edu.
Submitted on March 14, 2006
Revised on September 15, 2006
Accepted on 2 November 2006
The success of mapping genes involved in complex diseases, using association or linkage disequilibrium methods, depends heavily on the number and frequency of susceptibility alleles of these genes. These methods will be economically and statistically feasible if common diseases are usually influenced by one or a few susceptibility alleles at each locus (common disease - common variant, CDCV, hypothesis), but not so if there is a high degree of allelic heterogeneity. Here, we use forward-time population simulations to investigate the impact of various genetic and demographic factors on the allelic spectra of human diseases, based on two models proposed by Reich and Lander, and by Pritchard. Factors considered are more complex demographies, finite allele mutation model, population structure and migration, and interaction between disease susceptibility loci. The conclusion is that the CDCV hypothesis holds and that the phenomenon is caused by transient effects of demography (population expansion). As a result, we devise a multilocus generalization of the Reich and Lander model and demonstrate how interaction between loci with respect to their response to selection may lead to complex effects. We discuss the implications for mapping of complex diseases.
Key Words: allelic spectrum, common disease common variant hypothesis, complex human disease, forward-time simulation
This article has been cited by other articles:
 |
|
 |
|
  M. Slatkin Exchangeable Models of Complex Inherited Diseases Genetics, August 1, 2008; 179(4): 2253 - 2261. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Padhukasahasram, P. Marjoram, J. D. Wall, C. D. Bustamante, and M. Nordborg Exploring Population Genetic Models With Recombination Using Efficient Forward-Time Simulations Genetics, April 1, 2008; 178(4): 2417 - 2427. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Hoggart, M. Chadeau-Hyam, T. G. Clark, R. Lampariello, J. C. Whittaker, M. De Iorio, and D. J. Balding Sequence-Level Population Simulations Over Large Genomic Regions Genetics, November 1, 2007; 177(3): 1725 - 1731. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. A. Wright, H. Huang, X. Guan, K. Gamiel, C. Jeffries, W. T. Barry, F. Pardo-Manuel de Villena, P. F. Sullivan, K. C. Wilhelmsen, and F. Zou Simulating association studies: a data-based resampling method for candidate regions or whole genome scans Bioinformatics, October 1, 2007; 23(19): 2581 - 2588. [Abstract] [Full Text] [PDF]
|
|